DESCRIPTION (Applicant's Description): Age-related macular degeneration (ARMD) is a progressive disorder of the retina occurring in people older than age 50 associated with vision loss coupled with a spectrum of specific clinical, physiological and histopathological features. The pathogenic mechanisms for these specific changes are unknown, but circumstantial evidence suggests a role for a macrophage-mediated component in ARMD. We propose the general hypothesis that choroidal macrophages observed in ARMD are blood-derived monocytes recruited to the choriocapillaris to scavenge debris and deposits trapped in Bruch's membrane. In this project, we propose two specific aims to explore macrophage activation under conditions relevant to ARMD. In aim 1, we will use freshly isolated blood monocytes from normal subjects or ARMD patients, to establish the existence of high and low activity monocytes and to determine if high activity is a prognostic marker for ARMD progression. In aim 2, using a mouse model for age-related subRPE extracellular deposit formation recently developed in our laboratory, we will induce high activity monocytes in mice and establish that these macrophages will increase the severity of RPE degeneration or rate of progression of deposit formation.